Risk factors for cancer from agricultural chemicals in the ambient environment are studied to estimate the contribution of these environmental exposures to cancer in the rural population. Rural populations in agricultural areas have exposures to pesticides and nitrates in drinking water that are intermediate between occupationally-exposed groups and the general population. Case-control studies have been conducted on non-Hodgkin's lymphoma and cancers of the brain, bladder, colon, rectum, stomach, esophagus, pancreas, and kidney. Databases of water contaminants, gathered for routine monitoring purposes, are being used to estimate past exposures via public water supplies to individuals in these case-control studies. Nitrate levels in public water supplies in Iowa were not associated with risk of bladder and pancreas cancer. However, higher intakes of dietary nitrite were associated with an increased risk of pancreas cancer. Overall, drinking water nitrate levels were not associated with risk of colon, rectal, and kidney cancer; however, specific subgroups with increased nitrosation ability were at increased risk of colon and kidney cancer. Elevated nitrate in public water supplies in Nebraska was not associated with risk of glioma. Elevated nitrate levels in public drinking water supplies were associated with an increased risk of non-Hodgkin's lymphoma in Nebraska. This hypothesis was investigated in a recently completed case-control investigation of non-Hodgkin's lymphoma. We found no overall association with the highest quartile of average drinking water nitrate (more than 2.90 mg/L nitrate-N: OR=1.2, 95% CI 0.6-2.2) or with years more than 5mg/L (10+ years: OR=1.4, 95% CI 0.7-2.9). We saw no evidence of an interaction between drinking water nitrate exposure and either vitamin C intake or red meat intake, an inhibitor and precursor, respectively, of in vivo NOC formation. The issue of nitrate as a cancer risk factor is being pursued further in an ecologic study of census-block groups in the Platte River Valley of Nebraska and Colorado, where elevated nitrate levels are among the highest in the country. Nitrate levels in private wells are being estimated using data on land cover, livestock feedlot locations, soil type, and other information. We are also developing new approaches, and improving existing methods, of exposure assessment in studies of general environmental exposures, with a primary focus on pesticides and nitrate. Geographic information systems (GIS) are being utilized for developing new approaches to estimating indirect exposure to pesticides and for estimating exposure to nitrate in private wells. Remote sensing data (satellite imagery) and historical records were used to estimate the population in Nebraska and Iowa potentially exposed to agricultural pesticides through the proximity of their homes to agricultural land treated with pesticides. First, a feasibility study in Nebraska demonstrated that using available data and a GIS accurate historical crop maps could be produced and that these could be linked to pesticide use data to estimate probabilities of indirect exposure to agricultural pesticides. A similar approach was used for Iowa participants of the case control study of NHL. It was determined that 58% of the study population lived within 500 meters of corn or soybeans fields. To validate this method, we compared agricultural pesticides measured in house dust samples to the proximity of homes from crop fields and found a significantly elevated herbicide concentrations in homes within 750 meters of corn or soybean fields. Further work in this area by our collaborators included the development of a method to automate crop mapping from satellite imagery. We are continuing to refine the GIS-based approach to estimating agricultural pesticide exposure by incorporating information from a pesticide primary drift model and factors affecting secondary drift. To improve exposure assessment for home and garden pesticides we developed and published a "pesticide-exposure matrix" that lists the active ingredients that were on the market to treat specific type of home and garden pests back through time. With collaborators in California, we are measuring levels of pesticides, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and metals in house dust samples from an ongoing case-control study of childhood leukemia in Northern California and the Central Valley. We compared concentrations of pesticides and other chemicals in dust samples collected by two methods, a specialized vacuum (the HVS3) and participant's own vacuum bag. Correlations were high (more than 0.80) for most analytes. With collaborators at Colorado State University, we are refining metrics to evalute agricultural pesticide use near residences, using information about the current and historical location of crops near residences. A comparison of a metric based solely on California's pesticide use reporting (PUR) database with a metric that incorporates information on the location of crops grown indicates that the PUR metric classifies a substantially greater number of homes as "exposed" compared with a crop-based metric. In the population-based case-control study of NHL in four centers, risk associated with exposure to home and garden insecticides was determined using two exposure measures: interview-derived information on insecticide use in current and previous residences (1321 cases, 1057 controls), and insecticide concentrations in carpet dust (682 cases, 513 controls). People whose homes were treated for termites had elevated NHL risk (odds ratio=1.3, 95% confidence interval=1.004-1.6). Risk was modestly elevated in all but one study center and in all sexes and races. The elevation in risk was restricted to people whose homes were treated before the 1988 ban on the termiticide chlordane. There was a significant trend of increasing risk with increasing levels of chlordane residues in dust (P trend=0.045) and a marginally significant trend for gamma-chlordane (P trend=0.06). We found no evidence of associations for insects overall, for specific types of insects other than termites, or for elevated residues of other insecticides. We concluded that chlordane treatment of homes for termites may increase NHL risk. We are analyzing whether polymorphisms in immune genes affect NHL risk from exposure to organochlorine pesticides, PCBs, and dioxins. Using a GIS, residential proximity to specific industries, hazardous waste sites, and specific chemical releases as reported by the Environmental Protection Agency's Toxic Release Inventory will be evaluated in an ongoing case control study of bladder cancer in New England.and in the multi-center case-control study of NHL. We evaluated the accuracy of geocoding methods for determining residential location in rural and urban areas by comparing geocoded addresses to global positioning system measurements. We also evaluated census factors and spatial clustering of respondents and nonrespondents in the NHL case-control. Spatial clustering could be explained by demographic differences between responders and nonresponders. Estimated bias in the association between educational level and NHL risk was small.